Blood heavy-metal levels and risk of hematologic cancer in u.S. adults: Nhanes 2021–2023

Abstract Blood Heavy-Metal Levels and Risk of Hematologic Cancer in U.S. Adults: NHANES 2021–2023 Background: Heavy metals—including lead, cadmium, mercury, manganese, and selenium—can generate reactive oxygen species, interfere with DNA repair, and dysregulate immune function, all of which are biologically plausible pathways for leukemogenesis and lymphomagenesis. While occupational cohorts have linked elevated metal exposure to increased leukemia or lymphoma risk, evidence in the general population is sparse and often relies on ecological measures rather than individual biomonitoring. The National Health and Nutrition Examination Survey (NHANES) routinely quantifies blood metal concentrations in a nationally representative sample, providing a unique opportunity to test whether environmental exposures correlate with hematologic cancer at the population level. We analysed data from NHANES (2021–2023) to identify if presence of heavy metals in the blood is associated with hematologic malignancies.. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2021–2023 were merged (analytic N = 8,727). Blood levels of lead (Pb), cadmium (Cd), total mercury (Hg-T), inorganic mercury (Hg-I), selenium (Se), and manganese (Mn) were examined. The outcome was any self-reported diagnosis of leukemia or Hodgkin lymphoma; participants reporting neither served as controls. Survey-weighted multivariable logistic regression estimated odds ratios (ORs) per interquartile-range increase in metal level, adjusting for age, sex, and race/ethnicity. Model discrimination was quantified with the area under the receiver-operating-characteristic curve (AUC) and calibration plots. Results: Hematologic cancer was reported by 15 % of participants. After adjustment, higher blood lead was associated with greater odds of cancer (OR = 1.27, 95 % CI 1.17–1.35, p < 0.001), whereas higher manganese was inversely associated (OR = 0.87, 95 % CI 0.81–0.94, p = 0.0005). Cadmium, total mercury, inorganic mercury, and selenium showed no significant associations. The multivariable model exhibited modest discrimination (AUC = 0.58) and tended to under-predict risk at higher probability ranges. Conclusion: In this nationally representative sample, elevated blood lead was positively and manganese inversely associated with self-reported hematologic malignancies. There was no significant association of hematologic malignancies with cadmium, selenium, total and inorganic mercury. While causal inference is limited by cross-sectional design and self-reporting, these findings underscore the need for further prospective, biomarker-based studies to clarify the etiologic role of environmental metal exposures in hematologic malignancies.